1. Preparations of isolated glomeruli were superfused and the effects of colchicine, the vinca alkaloids, and the cytochalasins A, B, D, and E investigated on basal renin release and the response of the glomeruli to osmotic stress. 2. Colchicine (10(-3) M) had no effect, whereas vinblastine and vincristine (10(-5) M) caused a progressive increase in basal renin release from isolated glomeruli. 3. After 60 min exposure to either colchicine or the vinca alkaloids, the first renin release response to a hypoosmotic challenge (reduction in sucrose or sodium chloride concentration) was depressed while that of the second (after 120 min exposure) was enhanced. 4. Addition of 0.5% dimethylsulphoxide (DMSO) and each of the cytochalasins A, B, D, and E (5 micrograms/ml.) had no significant effect on basal renin release. 5. DMSO (0.5%) depressed the release response to the first 20 m-osmole/kg reduction in medium osmolality obtained by lowering the sucrose concentration. This effect had vanished at the time of the second 20 m-osmole stimulus (120 min). 6. The normal response to the first 30 m-osmole/kg reduction in NaCl concentration (and medium osmolality) was abolished by 0.5% DMSO. Rather, a depressed release compared to unstimulated control experiments was observed. The response to the second stimulus in the presence of DMSO was about half that of control experiments. 7. Following the first hypoosmotic stimulus (by lowering the concentrations of sucrose of NaCl) the cytochalasins A, B, D and E (5 micrograms/ml.) caused an increased release of renin which persisted throughout the length of the experiment. The cytochalasins used were equally potent in this respect. 8. The results are in agreement with previous findings, suggesting that renin release from the juxtaglomerular cells adhering to isolated glomeruli is mediated through a mechanism different from exocytosis.